Cerebral blood flow and cerebral metabolism will be studied longitudinally in an experimental animal model of atherosclerotic cerebral vascular disease. Despite the magnitude of the clinical problem, and the importance of stroke prevention, little is known of the sequence and course of early changes of cerebral vasculature and circulation which precede stroke. The experiments proposed involve a collaboration among physiologists, animal pathologists, and neuropathologists. In non-human primates fed an atherogenic diet, preliminary evidence indicates that both systemic atherosclerosis and abnormalities in cerebral blood flow response to hypercarbia and hypoxia can be elicited by 16-24 months. Cerebral blood flow and metabolism will be studied in dietfed and control monkeys at 12 and 24 months. At necropsy the entire vasculature, including the extra- and intracranial cerebral vessels will be carefully studied by histological methods. The perfusion-fixed brain will be examined for ischemic changes. The locus and severity of vascular changes will be correlated with physiological studies and neuropathology findings in each animal. From such interrelationships, predictive criteria for pre-clinical cerebral vascular disease may be developed. Our ultimate objective is a better understanding of both stroke risk and stroke pathogenesis in man.